Psoriasis like phenotype in K5.Stat3C transgenic mice depends on the IL-23/Th17 axis through interleukin 36R signals

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461695
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Kochi University
• Principal Investigator: OHKO Kentaro 高知大学, 教育研究部医療学系臨床医学部門, 助教 (90595274)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 乾癬 / IL-36 / 膿疱

Outline of Final Research Achievements

Psoriasis is a common chronic inflammatory skin disease. Recently, the IL-1 family members Interleukin-36, IL-36alpha, IL-36beta, IL-36gamma and the receptor antagonist IL-36Ra, constitute a novel signaling system that is poorly understood. First, we verified that psoriatic lesions showed increased levels of IL-36 ligands. Next, psoriasis like lesions in this K5.Stat3C mice showed increased transcriptional levels of the IL36A, IL36B, IL36G and IL36RN. To verify whether IL-36R deficiency attenuated psoriasis-like lesion of mice model, we generated IL-36R(-/-):K5.Stat3C mice. Strikingly, IL-36R deficiency markedly attenuated TPA-induced skin lesion, regarding ear thickness and histology. In addition, IL-23p19, and other signature molecules related with psoriasis were down-regulated. Finally, experiments using primary kerarinocytes(KC), dendric cells(DC) and bone marrow chimera mice, revealed that the IL-36 signalings of both KCs and DCs contributed to development of psoriatic lesion.

Free Research Field

乾癬